ABSTRACT Many disease processes cause bodily tissues to experience high friction and concomitant pain, including dry eye, vaginal dryness, and osteoarthritis. Thus, there is an unmet clinical need for new biomaterial-based lubricants. Of these diseases, osteoarthritis (OA) is a complex disease that afflicts approximately 30 million Americans and 50% of all people ?65 years. OA occurs due to progressive break down of articular cartilage, the tissue that distributes loads applied to articulating joints. Specifically associated with OA is a deterioration of the lubricating properties of the synovial fluid; this deterioration arises from the synovial fluid?s naturally- occurring hyaluronic acid (HA) becoming lower molecular weight and a loss of the glycoprotein lubricin. This renders the cartilage prone to further wear, along with increased patient pain and reduced mobility, until a total knee replacement surgery is required. Viscosupplementation, the intra-articular injection of HA, is one treatment which has a US market of $1 billion ($2 billion globally). However, HA exhibits a short residence time in the joint (as it is rapidly degraded and cleared) and there are conflicting reports of HA?s efficacy in protecting the articular cartilage. Consequently, the leading US orthopedic society no longer recommends its use. To address this unmet patient need, we have developed a non-HA injectable medical device lubricant that: 1) is a bio-inspired synthetic polymer rather than HA and therefore is not susceptible to rapid enzymatic degradation, 2) is crosslinked into a large macromolecular network to significantly slow diffusion out of the joint and dramatically lengthen residence time, and 3) demonstrates reduction in friction and wear (i.e., protection) of ex vivo cartilage, whereas existing viscosupplement products have not been shown to protect cartilage. Our preliminary data demonstrating protection of cartilage and long residence time, along with the proposed class of polymer?s history of use in FDA-approved devices, support the promising potential of this bioinspired synthetic material as a novel lubricant. The aims of this proposal are: Specific Aim 1: Determine the mechanism of lubrication of novel lubricants. Specific Aim 2: Develop product specifications and scale-up pMPC synthesis (10g to 500g scale). Specific Aim 3: Evaluate lubricant cyto- and whole organ tissue compatibility with six relevant cell lines and with clearance organs of rats previously injected intraarticularly with lubricant. Development Plan. Successful completion of Aims 1-3 will de-risk and add value to this patent-pending technology, enabling further development (Phase II SBIR) to assess large animal efficacy and biocompatibility (ISO 10993 and pharmacokinetics studies) to apply for an Investigational Device Exemption. This technology will be highly attractive to major orthopedic companies as a thoroughly developed OA injectables market (physician training, marketability, reimbursement) already exists, making this product readily adoptable.